A conversation about misconduct in Alzheimer’s research, which first came to light in 2022, has recently reemerged in the media.
The allegations pertain to specific Alzheimer’s researchers and their publications, most often demonstrating evidence of image manipulation. Most famously, a now-retracted 2006 study in the US, which claimed to discover a particular sub-form of amyloid responsible for memory impairments.
What does this mean for Alzheimer’s research?
These allegations are concerning, and any indication of misconduct should be taken seriously.
Research integrity is at the heart of all impactful science – we, at the UK Dementia Research Institute, condemn any scientific misconduct, which has no place in research. Deliberate acts to falsify data and results undermine the scientific process and can have costly consequences.
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However, any instances of fraud or misconduct do not negate important and well performed research into the role of amyloid in Alzheimer’s, which is supported by extensive evidence from scientists worldwide. There is strong genetic evidence supporting the amyloid theory. An early study into the inherited form of Alzheimer’s found that family members had a mutation in the gene that codes for amyloid.
Has the field been too focused on amyloid?
It is important to look beyond amyloid and challenge the idea that there is a single cause initiating and driving Alzheimer’s disease. Thinking has evolved since the amyloid theory was first described decades ago, and the vast majority of researchers now support a broader picture of multiple different drivers of the disease. An approach reflected in the portfolio of potential therapeutics currently in trials – 18% of drugs in the clinical trial pipeline last year targeted amyloid, with most research exploring other pathways and processes1.
At the UK DRI, our scientists are exploring multiple approaches to understanding and treating dementia, and making exciting, widespread discoveries. For example, Prof Will McEwan and team are investigating ways to selectively target tau, another protein implicated in Alzheimer’s, by harnessing molecules involved in the immune system. Prof Tara Spires-Jones aims to understand why synapses, the connections between brain cells, are lost in Alzheimer’s, and whether boosting their resilience could protect the brain. Prof Sir David Klenerman recently developed a new test to detect and measure inflammation in the brain, a key hallmark of Alzheimer’s which proceeds clinical symptoms. This could improve diagnostics and help test new therapies in clinical trials.
Why are anti-amyloid drugs the only ones available in the clinic?
Amyloid-targeting treatments are the only type of drug to have shown effectiveness in phase 3 clinical trials for Alzheimer’s so far, however this does not mean that no other types of treatment have been considered or evaluated. In 2019, it was reported that 99% of Alzheimer’s clinical trials, encompassing a wide range of targets, had so far failed2. Many other types of treatment have been tested and unfortunately failed to progress to advanced clinical trial stages.
The timeline for a new drug to be developed, pass through the rigorous testing requirements, and enter the clinic spans more than a decade, and costs many millions of pounds. With scientists continuing to explore a wide variety of treatment avenues, the field is hopeful we will find new and effective ways to combat neurodegenerative disease.
The field of dementia research remains robust, with thousands of researchers worldwide publishing tens of thousands of papers last year alone. Rare incidences of scientific misconduct should not overshadow the significant progress being made in understanding and treating dementia.
What is the UK DRI doing to boost research integrity?
As part of continuing efforts to ensure the quality of research conducted by UK DRI, last year we invited Prof Malcolm Macleod, a leading expert in research quality and research integrity, to help us with this work.
He has met with all UK DRI Centre Directors to understand the type of research being carried out, particular challenges they face, and their approach to ensuring research quality. He is now conducting in person visits to UK DRI centres, to provide training and education on opportunities to further improve research practices.
In related work, UK DRI will shortly launch an online training portal providing continuing professional development materials. We are working with colleagues to develop tools to pre-screen submitted manuscripts to identify ways in which they might be improved, for instance by more complete descriptions of experimental procedures and materials.
Of course, every research performing organisation has some things which it could do better, but I have been impressed by the commitment to improvement, and to the willingness to recognise that there are things which might be improved. In my experience, organisations which don't recognise these things, which assert that there is no chance of things going wrong, are the most likely to run into trouble.
Prof Malcolm MacLeod
Scientific misconduct is unacceptable, and the UK DRI takes any allegations seriously. While these instances are rare, they can have disproportionate consequences. Ensuring research integrity is a broader priority – this means fostering transparency, reproducibility, and ethical conduct across all our work. We are committed to upholding the highest standards through rigorous policies, training, and a culture that values responsible research practices.
References:
1. Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer's disease drug development pipeline: 2024. Alzheimers Dement (N Y). 2024 Apr 24;10(2):e12465. doi: 10.1002/trc2.12465.
2. Cummings, J., Feldman, H.H. & Scheltens, P. The “rights” of precision drug development for Alzheimer’s disease. Alz Res Therapy 11, 76 (2019). https://doi.org/10.1186/s13195-019-0529-5
Image credit: D Martin